Lithium modulates the production of peripheral and cerebral cytokines in an animal model of mania induced by dextroamphetamine.

Abstract

OBJECTIVES:

Several recent studies have suggested that the physiopathology of bipolar disorder (BD) is related to immune system alterations and inflammation. Lithium (Li) is a mood stabilizer that is considered the first-line treatment for this mood disorder. The goal of the present study was to investigate the effects of Li administration on behavior and cytokine levels [interleukin (IL)-1β, IL-4, IL-6, IL-10, and tumor necrosis factor-alpha (TNF-α)] in the periphery and brains of rats subjected to an animal model of mania induced by amphetamine (d-AMPH).

METHODS:

Male Wistar rats were treated with d-AMPH or saline (Sal) for 14 days; on Day 8 of treatment, the rats were administered Li or Sal for the final seven days. Cytokine (IL-1β, IL-4, IL-6, IL-10, and TNF-α) levels were evaluated in the cerebrospinal fluid (CSF), serum, frontal cortex, striatum, and hippocampus.

RESULTS:

The present study showed that d-AMPH induced hyperactivity in rats (p < 0.001), and Li treatment reversed this behavioral alteration (p < 0.001). In addition, d-AMPH increased the levels of IL-4, IL-6, IL-10, and TNF-α in the frontal cortex (p < 0.001), striatum (p < 0.001), and serum (p < 0.001), and treatment with Li reversed these cytokine alterations (p < 0.001).

CONCLUSIONS:

Li modulates peripheral and cerebral cytokine production in an animal model of mania induced by d-AMPH, suggesting that its action on the inflammatory system may contribute to its therapeutic efficacy.

• Authors: Samira S Valvassori, Paula T Tonin, Roger B Varela, André F Carvalho, Edemilson Mariot, Rafaela T Amboni, Guilherme Bianchini, Monica L Andersen, João Quevedo
• Journal: Bipolar disorders (Bipolar Disord) Vol. 17 Issue 5 Pg. 507-17 (Aug 2015) ISSN: 1399-5618 [Electronic] Denmark
• PMID: 25929806 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Antimanic Agents
• Central Nervous System Stimulants
• Cytokines
• IL1B protein, rat
• Interleukin-1beta
• Interleukin-6
• Lithium Compounds
• Tumor Necrosis Factor-alpha
• Interleukin-10
• Interleukin-4
• Dextroamphetamine

Topics

• Animals
• Antimanic Agents (pharmacology, therapeutic use)
• Behavior, Animal (drug effects)
• Bipolar Disorder (chemically induced, drug therapy, immunology)
• Brain (drug effects, immunology)
• Central Nervous System Stimulants (toxicity)
• Cytokines (cerebrospinal fluid, drug effects, immunology)
• Dextroamphetamine (toxicity)
• Disease Models, Animal
• Frontal Lobe (drug effects, immunology)
• Hippocampus (drug effects, immunology)
• Hyperkinesis (chemically induced, drug therapy, immunology)
• Interleukin-10 (cerebrospinal fluid, immunology)
• Interleukin-1beta (cerebrospinal fluid, drug effects, immunology)
• Interleukin-4 (cerebrospinal fluid, immunology)
• Interleukin-6 (cerebrospinal fluid, immunology)
• Lithium Compounds (pharmacology, therapeutic use)
• Male
• Motor Activity (drug effects, immunology)
• Neostriatum (drug effects, immunology)
• Rats
• Rats, Wistar
• Tumor Necrosis Factor-alpha (cerebrospinal fluid, drug effects, immunology)